Polarisation gratings were generated using LCD screens with removed polarisers and the orientation of polarisation was changed by rotating the screen. Reaction to the stimulus was recorded using a fixation reflex. We show that, in agreement with the theoretical predictions, the maximum contrast sensitivity is achieved at horizontal and vertical orientations of polarisation. Our results demonstrate that the dependence of polarisation contrast sensitivity on the angle of polarisation can be analysed in the same way as the dependence of colour thresholds on wavelength of monochromatic light added to a grey background.

Persons with childhood experiences of out-of-home care (OHC) have elevated risks of having their own children taken into societal care. High educational attainment has been linked to favorable long-term outcomes in a host of previous studies on OHC alumni. This could be indicative of resilience, which may also have protective potential against intergenerational continuity of OHC placements.

The present study examined the processes of mediation and interaction by educational attainment, here conceptualized as having completed upper secondary school, regarding the intergenerational transmission of placement in OHC.

Longitudinal data came from a Swedish cohort of parents (and their children) born in 1953 (n=11,338).

Associations between parental experience of OHC and their children’s placement in OHC were analyzed by means of binary logistic regression. Four-way decomposition was used to explore mediation and interaction by parental educational attainment.

The odds of having at least one child being placed in OHC was more than six-fold (OR=6.67, 95% CI=5.28; 8.06) in the OHC group compared to majority population peers. Mediation and/or interaction by educational attainment accounted for a substantial proportion of the overall association (53%). Interaction effects appeared to be more important for the outcome than mediation.

Having completed upper secondary school seems to reflect processes of resilience with the potential to break the intergenerational transmission of placement in OHC. These findings suggest that the impact of enhanced educational attainment of OHC populations may have potential of extending into the fate of the next generation.

Having completed upper secondary school seems to reflect processes of resilience with the potential to break the intergenerational transmission of placement in OHC. These findings suggest that the impact of enhanced educational attainment of OHC populations may have potential of extending into the fate of the next generation.

Accurate detection of vessel bifurcation points from mesoscopic whole-brain images plays an important role in reconstructing cerebrovascular networks and understanding the pathogenesis of brain diseases. Existing detection methods are either less accurate or inefficient. In this paper, we propose VBNet, an end-to-end, one-stage neural network to detect vessel bifurcation points in 3D images.

Firstly, we designed a 3D convolutional neural network (CNN), which input a 3D image and output the coordinates of bifurcation points in this image. The network contains a two-scale architecture to detect large bifurcation points and small bifurcation points, respectively, which takes into account the accuracy and efficiency of detection. Then, to solve the problem of low accuracycaused by the imbalance between the numbers of large bifurcations and small bifurcations, we designed a weighted loss function based on the radius distribution of blood vessels. Finally, we extended the method to detect bifurcation points in 3D biomedical images.

Thermal ablation of tumors plays a key role to fight cancer, since it is a minimally invasive treatment which involves some advantages compared to surgery and chemotherapy, such as shorter hospital stays and consequently lower costs, along with minor side effects. In this context, computational modeling of heat transfer during thermal ablation is relevant to accurately predict the obtained ablation zone in order to avoid tumor recurrence risk caused by incomplete ablation, and the same time to save the surrounding healthy tissue. The aim of this work is to develop a more realistic porous media-based mathematical model to simulate a microwave thermal ablation (MWA) of an in vivo liver tumor surrounded by healthy tissue.

The domain is made up of a spherical tumor bounded by a cylindrical healthy liver tissue. The simulated microwave antenna is a 14G HS Amica-Gen Probe, and the supplied power of 60W is applied for 300s and 600s. The model consists in coupling modified Local Thermal Non Equilibrium (LTNE) equccurately tumor MWA, by considering increasingly realistic features, avoiding tumor recurrence, and improving both medical protocols and devices.

In this work, an in vivo microwave ablation of liver tumor surrounded by healthy tissue is modeled with a variable-porosity medium approach based on experimental measures. The outcomes shown for distinct vascularizations underline the key relevance of modeling more and more accurately tumor MWA, by considering increasingly realistic features, avoiding tumor recurrence, and improving both medical protocols and devices.

Photoacoustic tomography (PAT) is capable of obtaining cross-sectional images of small animals that represent the optical absorption of biological tissues. The multispectral Interlaced Sparse Sampling PAT, or ISS-PAT, is a previously proposed PAT imaging method that offered high quality images with much sparser transducer angular coverage. Although it provides superior imaging performance, the original ISS-PAT method suffered from a heavy computation burden, which hinders its practical application.

Here, we propose a new regularization scheme based on the directional total variation (dTV) for ISS-PAT. This method efficiently imposes the structural information by considering both the edge position and direction information of the anatomical prior image in ISS-PAT. It does not require image segmentation, and can be conveniently solved by a modified alternating direction of multipliers (ADMM) algorithm.

We perform simulation, tissue mimicking phantom and in vivo small animal experiments to evaluate the proposed scheme. The reconstructed PAT images showed image quality and spectral un-mixing accuracy close to those obtained by non-local means based ISS-PAT, but with much shorter image reconstruction time. For a 1/6 sparse sampling rate, the average efficiency improvement is nearly 16-folds.

The experimental results demonstrate the feasibility of the dTV regularization scheme for ISS-PAT. Its efficient image reconstruction performance facilitates the potential of the hardware realization and practical applications of the ISS-PAT.

The experimental results demonstrate the feasibility of the dTV regularization scheme for ISS-PAT. Its efficient image reconstruction performance facilitates the potential of the hardware realization and practical applications of the ISS-PAT.Calonectris diomedea is a colonial Procellariiform breeding on Mediterranean islands. The stomach oil produced during chick rearing is a peculiar trait of this species. The composition of the stomach oil is likely to reflect the composition of the prey ingested and might reveal the contaminants uptake with prey becoming a possible tool for the marine pollution monitoring. We examined the concentration of 15 trace elements by ICP-MS and direct mercury analyser. The principal component analysis revealed a heterogeneous pattern of metal concentration, showing a significant separation between samples collected 20 and 70 days after hatching. The data obtained in this work give preliminary information on the feeding habits and breeding ecology of Linosa’s colony of Scopoli’s shearwater. The trace metals variability found suggest that the stomach oil may have a role as trophic markers to understand predator-prey relationships and to have evidence on the accumulation of pollutants in the latter.Does underage access to alcohol increase teenage drinking and crime? To address this question, I leverage a discontinuity in legal access to alcohol at age 16 in Germany, a country with high consumption levels and a particularly early access regulation. Using detailed survey data and administrative crime records from 2005 to 2015, I detect considerable increases in drinking participation, frequency, and intensity at the legal cutoff along the middle and lower end of the distribution. These increases coincide with discrete jumps in criminal engagement under the influence of alcohol, mostly due to violent and property crimes. My findings suggest that changes in drinking intensity induce these crimes, implying a drinking-crime elasticity of 0.4 at age 16.

Hospital readmissions and outpatient visits contribute to the significant burden on healthcare systems. Obstructive sleep apnea (OSA) is a chronic medical condition that is associated with cardiovascular comorbidities and other chronic conditions. Inpatient and outpatient healthcare utilization rates in patients with OSA following hospitalization are unclear.

This. retrospective case-control cohort study utilized a nationwide database to assess if OSA is associated with higher healthcare utilization post-hospitalization. We compared healthcare utilization among patients with OSA versus without OSA between 2009 and 2014 after matching for demographic variables, geographic location, hospital environment, reason for admission, and severity of illness during hospitalization. We measured future healthcare utilization by the number of ICU admissions, hospital admissions, emergency room visits, and outpatient visits after being discharged from the index hospitalization.

Two equal-sized cohorts comprised of 85,s and investigate the impact of directing additional resources to inpatients with OSA.To properly manage municipal solid waste (MSW) and meet the country’s biogas target, it is necessary for the government to prioritize their support to areas/provinces that have high resource potential. Therefore, this work designed a holistic approach for nationwide area-based organic MSW to biogas potential estimation. The total biogas power potential was ranged from 999 MW in 2021 to 1,652 MW in 2037. Moreover, priority setting on area-based biogas implementation was proposed, based on its resource potential to efficiently promote such technology. To achieve current biogas target of the country, the study identified 28% of national area coverage as priorities for actual execution, which could offset averagely 3% per year. To support design and planning purposes, an area with around 45,000 capita is recommended for developing 1 MW of MSW to biogas power plant using anaerobic digestion technology. The methodology development from this research revealed the link between resource potential and area-based prioritization framework that could be adopted in any growing economies to couple waste management with renewable energy production.Chemical Exchange Saturation Transfer (CEST) is a powerful technique for metabolic imaging, capable of exploring concentrations in the μM to mM range. However, extracting quantitative information from Z-spectra can be challenging due to the non-CEST contributions present and the limited knowledge about the exchanging pools. The PEAKIT tool is proposed as an alternative approach to quantifying CEST peaks, which requires no prior assumptions about the frequency offset or the underlying shape of the baseline. Specifically, the tool takes as input an experimental Z-spectrum and proceeds to identify peak candidates. After a baseline estimation based on Gaussian Process regression, PEAKIT outputs the chemical shift offsets, the areas, the heights and the statistical significance of the detected peaks. The performance and limitations of the PEAKIT tool are discussed for in vitro and in vivo applications.When considered separately from cardiovascular disease, stroke is the third leading cause of death in the U.S. and is the leading cause of long-term disability in adults. New approaches that can be offered to the majority of ischemic stroke patients, can be continued throughout post-stroke care, can limit stroke severity, and can complement or even enhance rehabilitation, would transform ischemic stroke recovery. The treatment of obstructive sleep apnea (OSA) in patients with acute ischemic stroke may represent one such approach. This manuscript reviews the epidemiologic studies of the bidirectional association between OSA and stroke, and the mechanisms and molecular signatures of OSA leading to transient ischemic attack and stroke as well as the randomized controlled trials and observational cohort studies examining continuous positive airway treatment efficacy on the impact of stroke outcomes. Finally, the insights these studies provide on future research are also discussed.The intracellular uptake concentration determines drug absorption, drug activity, and toxicity. Sesamol, sesamin, and sesamolin are promising bioactive components from Sesame indicum L. Their respective intracellular uptake pathway and cytotoxicity were evaluated using melanoma and non-cancerous cells. Quantitative structure-activity relationship (QSAR) models were built to identify the molecular features affecting drug uptake in cells. The respective intracellular uptake pathway for sesamol vs. sesamin and sesamolin was carrier-mediated vs. passive transport. Topological polar surface area (PSA) and 2D autocorrections increase the intracellular concentration (C/M ratio) of these compounds. Sesamol has the lowest C/M ratio compared to sesamin and sesamolin, but only sesamol inhibits the cell viability of melanoma and provides an inhibition concentration at 50% (IC50) against melanoma cells. The slightly aqueous solubility of sesamin and sesamolin, therefore, limits testing of their cytotoxicity. In conclusion, sesamol has the potential to inhibit melanoma cell growth, but requires improvement of the C/M ratio to increase its physicochemical properties. Thus, in order to investigate the cytotoxicity of sesamin and sesamolin against melanoma cells a solubility enhancer is needed.The therapeutic armamentarium for the treatment of oral mucositis is very poor. Catechin and baicalin are two natural flavonoids that have been individually reported to have a curative potential. Flavocoxid is a mixed extract containing baicalin and catechin showing antioxidant effects and anti-inflammatory activity mainly due to a dual inhibition of inducible cyclooxygenase (COX-2), 5-lipoxygenase (5-LOX) and NLRP3 pathway. The aim of this study was to evaluate the anti-inflammatory and anti-oxidant effects of flavocoxid in an „in vitro” model of oral mucositis induced by triggering an inflammatory phenotype in human gingival fibroblasts (GF) and human oral mucosal epithelial cells (EC). GF and EC were challenged with lipopolysaccharide (LPS 2 μg/ml) alone or in combination with flavocoxid (32 μg/ml). Flavocoxid increased Nrf2, prompted a marked reduction in malondialdehyde levels and reduced the expression of COX-2 and 5-LOX together with PGE2, and LTB4 levels. Flavocoxid caused also a great decrease in the expression of NF-κB and turned off NLRP3 inflammasome and its downstream effectors signal, as caspase-1, IL-1β and IL-18 in both GF and EC cells stimulated with LPS. These results suggest a correlation between oxidative stress and NLRP3 activation and indicate that flavocoxid suppresses the inflammatory storm that accompanies oral mucositis. This preclinical evidence deserves to be confirmed in a clinical setting.Human fibroblast growth factor 19 (FGF19) has become a potential therapeutic target for metabolic-related diseases. However, the effects of FGF19 on obesity-induced bone loss have not been completely elucidated. The aim of this study was to investigate the protective effects of FGF19 in high-fat diet (HFD)-fed obese mice and palmitic acid (PA)-treated osteoblasts and to further explore its underlying mechanisms. In vivo, we found that FGF19 alleviated the decreased bone mineral density (BMD) induced by HFD. Micro-CT analysis of femur samples and histological analysis indicated that FGF19 alleviated HFD-induced loss of bone trabeculae and damage to the bone trabecular structure. In vitro, the results suggested that FGF19 ameliorated the PA-induced decline in osteoblast proliferation, increased cell death and impaired cell morphology. Additionally, FGF19 protected against the decline in activation of alkaline phosphatase (ALP) and protein expression of Collagen-1, Runx-2, and osteopontin (OPN) induced by PA. Furthermore, FGF19 might enhance osteogenic differentiation via the Wnt/β-catenin pathway and inhibit osteoclastogenesis by regulating the osteoprotegerin (OPG)/receptor activator of NF-κB ligand (RANKL) axis, thus attenuating the negative effect of PA in osteoblasts. In conclusion, our results suggested that FGF19 might promote osteogenic differentiation partially through activation of the Wnt/β-catenin pathway and alleviate obesity-induced bone loss.Metabolic reprogramming is a potential hallmark of tumor cells to support continuous proliferation. Metabolic heterogeneity in breast cancer patients has been highlighted as the driving cause of tumor progression and resistance to anticancer drugs. Studying and identifying distinct metabolic alterations in breast cancer subtypes could offer new perspectives for faster diagnosis and treatment. Given cancer cell dependency on glycolysis, the primary energy source, this enzymatic pathway will play a critical role in targeting therapies. Knowledge about the specific metabolic dependencies of tumors for growth and proliferation can be promising for novel targeted and cell-based therapies. Here, the metabolic status with emphasis on glycolysis of breast cancer cell lines according to their classification was reviewed.Spinal cord injury (SCI) is a central nervous system (CNS) devastate event that is commonly caused by traumatic or non-traumatic events. The reinnervation of spinal cord axons is hampered through a myriad of devices counting on the damaged myelin, inflammation, glial scar, and defective inhibitory molecules. Unfortunately, an effective treatment to completely repair SCI and improve functional recovery has not been found. In this regard, strategies such as using cells, biomaterials, biomolecules, and drugs have been reported to be effective for SCI recovery. Furthermore, recent advances in combinatorial treatments, which address various aspects of SCI pathophysiology, provide optimistic outcomes for spinal cord regeneration. According to the global importance of SCI, the goal of this article review is to provide an overview of the pathophysiology of SCI, with an emphasis on the latest modes of intervention and current advanced approaches for the treatment of SCI, in conjunction with an assessment of combinatorial approaches in preclinical and clinical trials. So, this article can give scientists and clinicians’ clues to help them better understand how to construct preclinical and clinical studies that could lead to a breakthrough in spinal cord regeneration.Brain tumors are responsible for high mortality and morbidity worldwide. The brain tumor treatment depends on identification of molecular pathways involved in progression and malignancy. Enhancer of zeste homolog 2 (EZH2) has obtained much attention in recent years in field of cancer therapy due to its aberrant expression and capacity in modulating expression of genes by binding to their promoter and affecting methylation status. The present review focuses on EZH2 signaling in brain tumors including glioma, glioblastoma, astrocytoma, ependymomas, medulloblastoma and brain rhabdoid tumors. EZH2 signaling mainly participates in increasing proliferation and invasion of cancer cells. However, in medulloblastoma, EZH2 demonstrates tumor-suppressor activity. Furthermore, EZH2 can regulate response of brain tumors to chemotherapy and radiotherapy. Various molecular pathways can function as upstream mediators of EZH2 in brain tumors including lncRNAs and miRNAs. Owing to its enzymatic activity, EZH2 can bind to promoter of target genes to induce methylation and affects their expression. EZH2 can be considered as an independent prognostic factor in brain tumors that its upregulation provides undesirable prognosis. Both anti-tumor agents and gene therapies such as siRNA have been developed for targeting EZH2 in cancer therapy.Despite the promising medicinal properties, berberine (BBR), due to its relatively poor solubility in plasma, low bio-stability and limited bioavailability is not used broadly in clinical stages. Due to these drawbacks, drug delivery systems (DDSs) based on nanoscale natural polysaccharides, are applied to address these concerns. Natural polymers are biodegradable, non-immunogenic, biocompatible, and non-toxic agents that are capable of trapping large amounts of hydrophobic compounds in relatively small volumes. The use of nanoscale natural polysaccharide improves the stability and pharmacokinetics of the small molecules and, consequently, increases the therapeutic effects and reduces the side effects of the small molecules. Therefore, this paper presents an overview of the different methods used for increasing the BBR solubility and bioavailability. Afterwards, the pharmacodynamic and pharmacokinetic of BBR nanostructures were discussed followed by the introduction of natural polysaccharides of plant (cyclodextrines, glucomannan), the shells of crustaceans (chitosan), and the cell wall of brown marine algae (alginate)-based origins used to improve the dissolution rate of poorly soluble BBR and their anticancer and antibacterial properties. Finally, the anticancer and antibacterial mechanisms of free BBR and BBR nanostructures were surveyed. In conclusion, this review may pave the way for providing some useful data in the development of BBR-based platforms for clinical applications.SARS-CoV-2 causes respiratory illness with a spectrum of systemic complications. However, the mechanism for cardiac infection and cardiomyocyte injury in COVID-19 patients remains unclear. The current literature supports the notion that SARS-CoV-2 particles access the heart either by the circulating blood cells or by extracellular vesicles, originating from the inflamed lungs, and encapsulating the virus along with its receptor (ACE2). Both cardiomyocytes and pericytes (coronary arteries) express the necessary accessory proteins for access of SARS-CoV-2 particles (i.e. ACE2, NRP-1, TMPRSS2, CD147, integrin α5β1, and CTSB/L). These proteins facilitate the SARS-CoV-2 interaction and entry into the pericytes and cardiomyocytes thus leading to cardiac manifestations. Subsequently, various signaling pathways are altered in the infected cardiomyocytes (i.e. increased ROS production, reduced contraction, impaired calcium homeostasis), causing cardiac dysfunction. The currently adopted pharmacotherapy in severe COVID-19 subjects exhibited side effects on the heart, often manifested by electrical abnormalities. Nonetheless, cardiovascular adverse repercussions have been associated with the advent of some of the SARS-CoV-2 vaccines with no clear mechanisms underlining these complications. We provide herein an overview of the pathways involved with cardiomyocyte in COVID-19 subjects to help promoting pharmacotherapies that can protect against SARS-CoV-2-induced cardiac injuries.Coronavirus disease 2019 (COVID-19) has a devastating impact on global populations triggered by a highly infectious viral sickness, produced by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The third major cause of mortality in the United States, following heart disease and cancer in 2020, was undoubtedly COVID-19. The centers for disease control and prevention (CDC) and the world health organization (WHO) separately developed a categorization system for differentiating new strains of SARS-CoV-2 into variants of concern (VoCs) and variants of interest (VoIs) with the continuing development of various strains SARS-CoV-2. By December 2021, five of the SARS-CoV-2 VoCs were discovered from the onset of the pandemic depending on the latest epidemiologic report by the WHO Alpha (B.1.1.7), Beta (B.1.351), Gamma (P.1), Delta (B.1.617.2), and Omicron (B.1.1.529). Mutations in the receptor-binding domain (RBD) and n-terminal domain (NTD) have been found throughout all five identified VoCs. All strains other than the delta mutant are often found with the N501Y mutation situated on the RBD, resulting in higher binding between the spike protein and angiotensin-converting enzyme 2 (ACE2) receptors, enhanced viral adhesion, and following the entrance to host cells. The introduction of these new strains of SRAS-CoV-2 is likely to overcome the remarkable achievements gained in restricting this viral disease to the point where it is presented with remarkable vaccine developments against COVID-19 and strong worldwide mass immunization initiatives. Throughout this literature review, the effectiveness of current COVID-19 vaccines for managing and prohibiting SARS-CoV-2 strains is thoroughly described.The emergence of clinical complications and therapeutic challenges for treating various diseases necessitate the discovery of novel restorative functional materials. Polymer-based drug delivery systems have been extensively reported in the last two decades. Recently, there has been an increasing interest in the progression of natural biopolymers based controlled therapeutic strategies, especially in drug delivery and tissue engineering applications. However, the solubility and functionalisation due to their complex network structure and intramolecular bonding seem challenging. This review explores the current advancement and prospects of the most promising natural polymers such as cellulose, starch and their derivatives-based drug delivery vehicles like hydrogels, films and composites, in combating major ailments such as bone infections, microbial infections, and cancers. In addition, selective drug targeting using metal-drug (MD) and MD-based polymeric missiles have been exciting but challenging for its application in cancer therapeutics. Owing to high biocompatibility of starch and cellulose, these materials have been extensively evaluated in biomedical and pharmaceutical applications. This review presents a detailed impression of the current trends for the construction of biopolymer-based tissue engineering, drug/gene/protein delivery vehicles.The growth and development of cancer are directly correlated to the suppression of the immune system. A major breakthrough in cancer immunotherapy depends on various mechanisms to detect immunosuppressive factors that inhibit anti-tumor immune responses. Immune checkpoints are expressed on many immune cells such as T-cells, regulatory B cells (Bregs), dendritic cells (DCs), natural killer cells (NKs), regulatory T (Tregs), M2-type macrophages, and myeloid-derived suppressor cells (MDSCs). Immune inhibitory molecules, including CTLA-4, TIM-3, TIGIT, PD-1, and LAG-3, normally inhibit immune responses via negatively regulating immune cell signaling pathways to prevent immune injury. However, the up-regulation of inhibitory immune checkpoints during tumor progression on immune cells suppresses anti-tumor immune responses and promotes immune escape in cancer. It has recently been indicated that cancer cells can up-regulate various pathways of the immune checkpoints. Therefore, targeting immune inhibitory molecules through antibodies or miRNAs is a promising therapeutic strategy and shows favorable results. Immune checkpoint inhibitors (ICIs) are introduced as a new immunotherapy strategy that enhance immune cell-induced antitumor responses in many patients. In this review, we highlighted the function of each immune checkpoint on different immune cells and therapeutic strategies aimed at using monoclonal antibodies and miRNAs against inhibitory receptors. We also discussed current challenges and future strategies for maximizing these FDA-approved immunosuppressants’ effectiveness and clinical success in cancer treatment.In the modeling of a simulated moving bed, several assumptions are considered, the key assumption is there are no radial concentration gradients based on perfect mixing. However, it is difficult to achieve perfect mixing because the injected flowrate of the bed is periodically changed in the process. In this study, the performance of the simulated moving bed process was analyzed when the injected flow such as the feed or desorbent stream was unevenly distributed. To this end, the distribution function of the injected flow was calculated and applied to the model. Two types of distribution functions were obtained using the experimental results of a previous study, and the simulation results were compared with classical modeling assuming perfect mixing. In the base case simulation, the purity was similar in all cases, the productivity was higher more than 5% in the even distribution case compared to the most uneven distribution case. The effect of distribution was analyzed through sensitivity analysis by changing the overall flow rate, switching time, bed length, and flow rate of sections 2 and 3. As a result, regardless of the distribution applied, the trends of the performance parameters were the same. However, the more uneven the distribution, the greater the difference in productivity, recovery, and desorbent consumption compared to the even distribution case. It was confirmed that the design that distributes the injected flow more evenly has a better performance.Spatial demonstratives (this and that in English) convey distance relative to speaker (within reach vs. out of reach) and object characteristics such as ownership. Previous studies indicate that object characteristics affect adult demonstrative choice, for example, greater use of this for owned objects. Here, production of spatial demonstratives was studied developmentally to identify when demonstrative production is sensitive to both distance and ownership. In two experiments, 7-year-olds, 11-year-olds, and adults completed an object location memory task, and a language task eliciting this or that to indicate an object. Results indicate that adult-like demonstrative production starts around 7 years of age and continues to develop beyond 11 years. Nonlinguistic spatial memory did not vary significantly across age groups. Spatial demonstratives encode both semantic and spatial object characteristics throughout development, revealing the fundamental importance of semantic factors for demonstrative production.The current study investigated preschoolers’ ingroup bias in predicting people’s sharing across contexts and its relation to second-order theory of mind (ToM) ability. In Experiment 1, 96 5- and 6-year-old children were assigned to one of two groups in a minimal group paradigm. They heard a story about fictional ingroup and outgroup peers sharing in a public or private condition and were asked to predict and evaluate their sharing behavior. Children predicted that ingroup peers would share more than outgroup peers and also showed ingroup bias in evaluation regardless of the equal actual sharing of ingroup and outgroup peers. Moreover, 6-year-olds displayed a flexible ingroup bias in predicting others’ sharing across conditions because they held such a bias only in public conditions and did not expect ingroup and outgroup peers to share differently in private conditions. Experiment 2 tested a new sample of 80 6-year-olds with the same sharing story and a second-order false belief task. Results showed that only 6-year-olds who fully passed the false belief task showed a flexible bias in predicting sharing across conditions. Results indicate that children’s ingroup bias in predicting others’ sharing is becoming flexible across contexts as they grow up and ToM skills contribute to the development of their increasingly sophisticated prosocial reasoning.A growing body of research has examined the role of individual differences in children’s selective trust. The current study was designed to explore how individual differences in theory of mind and hostile attribution bias affect children’s trust. Four- and five-year-old children took part in a standard selective trust paradigm in which they had the choice between a previously inaccurate informant and an unfamiliar informant. They were also asked to interpret why the previously inaccurate informant had provided incorrect information in the past. Finally, children completed a hostile attribution bias task and a theory of mind task. Children with better theory of mind ability were more likely to defer to the unfamiliar informant on the selective trust task. Children with greater hostile attribution bias were more likely to interpret previous inaccuracy as a result of „being tricky” rather than having „made a mistake.” However, these interpretations did not influence children’s choices on the selective trust task. Therefore, although there is reason to believe that establishing selective trust involves both cognitive and social processes, the current study raises questions about the nature of this relationship and how children draw on different sociocognitive skills when establishing epistemic trust.RIPK1 plays a key role in the necroptosis pathway that regulates inflammatory signaling and cell death in various diseases, including inflammatory and neurodegenerative diseases. Herein, we report a series of potent RIPK1 inhibitors, represented by compound 70. Compound 70 efficiently blocks necroptosis induced by TNFα in both human and mouse cells (EC50 = 17-30 nM). Biophysical assay demonstrates that compound 70 potently binds to RIPK1 (Kd = 9.2 nM), but not RIPK3 (Kd > 10,000 nM). Importantly, compound 70 exhibits greatly improved metabolic stability in human and rat liver microsomes compared to compound 6 (PK68), a RIPK1 inhibitor reported in our previous work. In addition, compound 70 displays high permeability in Caco-2 cells and excellent in vitro safety profiles in hERG and CYP assays. Moreover, pre-treatment of 70 significantly ameliorates hypothermia and lethal shock in SIRS mice model. Lastly, compound 70 possesses favorable pharmacokinetic parameters with moderate clearance and good oral bioavailability in SD rat. Taken together, our work supports 70 as a potent RIPK1 inhibitor and highlights its potential as a prototypical lead for further development in necroptosis-associated inflammatory disorders.The RAS-RAF-MEK-ERK signaling pathway plays a key role to regulate multiple cellular functions. Acquired resistance to the first-generation RAF inhibitors that only targeted the bRAFV600E mutation prompted the need for a new generation of RAF inhibitors to target cancers bearing mutant RAS and wild type RAF activity by inhibition of paradoxical activation. Starting from the company’s previously reported RAF inhibitor 1, extensive drug potency and drug-like properties optimizations led to the discovery of molecule 33 (SHR902275) with greatly improved in vitro potency and solubility. Molecule 33 exhibited good DMPK (Drug Metabolism and Pharmacokinetics) properties, excellent permeability, and outstanding mouse/rat oral PK. It was further evaluated in an in vivo RAS mutant Calu6 xenograft mouse model and demonstrated dose dependent efficacy. To achieve high exposure in a toxicity study, pro-drug 48 was also explored.This work addresses the problem of cross-modality inference (CMI), i.e., inferring missing data of unavailable perceptual modalities (e.g., sound) using data from available perceptual modalities (e.g., image). We overview single-modality variational autoencoder methods and discuss three problems of computational cross-modality inference, arising from recent developments in multimodal generative models. Inspired by neural mechanisms of human recognition, we contribute the Nexus model, a novel hierarchical generative model that can learn a multimodal representation of an arbitrary number of modalities in an unsupervised way. By exploiting hierarchical representation levels, Nexus is able to generate high-quality, coherent data of missing modalities given any subset of available modalities. To evaluate CMI in a natural scenario with a high number of modalities, we contribute the „Multimodal Handwritten Digit” (MHD) dataset, a novel benchmark dataset that combines image, motion, sound and label information from digit handwriting. We access the key role of hierarchy in enabling high-quality samples during cross-modality inference and discuss how a novel training scheme enables Nexus to learn a multimodal representation robust to missing modalities at test time. Our results show that Nexus outperforms current state-of-the-art multimodal generative models in regards to their cross-modality inference capabilities.LOBSTER (LOss-Based SensiTivity rEgulaRization) is a method for training neural networks having a sparse topology. Let the sensitivity of a network parameter be the variation of the loss function with respect to the variation of the parameter. Parameters with low sensitivity, i.e. having little impact on the loss when perturbed, are shrunk and then pruned to sparsify the network. Our method allows to train a network from scratch, i.e. without preliminary learning or rewinding. Experiments on multiple architectures and datasets show competitive compression ratios with minimal computational overhead.Understanding adenovirus assembly and disassembly poses many challenges due to the virion complexity. A distinctive feature of adenoviruses is the large amount of virus-encoded proteins packed together with the dsDNA genome. Cryo-electron microscopy (cryo-EM) structures are broadening our understanding of capsid variability along evolution, but little is known about the organization of the non-icosahedral nucleoproteic core and its influence in adenovirus function. Atomic force microscopy (AFM) probes the biomechanics of virus particles, while simultaneously inducing and monitoring their disassembly in real time. Synergistic combination of AFM with EM shows that core proteins play unexpected key roles in maturation and entry, and uncoating dynamics are finely tuned to ensure genome release at the appropriate time and place for successful infection.Human respiratory coronaviruses (HCoVs), including the recently emerged SARS-CoV-2, the causative agent of the coronavirus disease 2019 (COVID-19) pandemic, potentially cause severe lung infections and multiple organ damages, emphasizing the urgent need for antiviral therapeutics and vaccines against HCoVs. Small animal models, especially mice, are ideal tools for deciphering the pathogenesis of HCoV infections as well as virus-induced immune responses, which is critical for antiviral drug development and vaccine design. In this review, we focus on the antiviral innate immune response, antibody response and T cell response in HCoV infected mouse models, and discuss the potential implications for understanding the anti-HCoV immunity and fighting the COVID-19 pandemic.

We investigated the safety and efficacy of the Numen coil compared with the Axium coil in the treatment of intracranial aneurysms.

Because CATCH (Coil Application Trial in China) is a prospective randomized controlled open-label noninferiority trial conducted in 10 centers across China, patients who fulfilled the inclusion and exclusion criteria were randomized 11 to either a test group (Numen) or a control group (Axium). The primary outcome was based on successful aneurysm occlusion at 6 months follow-up, whereas secondary outcomes included technical success, the recanalization and retreatment rates, and the rate of serious adverse events (SAEs) at 6 months and 12 months follow-up.

Between August 2017 and December 2019, 350 patients presenting with 350 aneurysms were enrolled and randomized. Per-protocol analysis showed that the successful aneurysm occlusion rate at 6 months was 91.18% for the test group compared with 91.85% inthe control group, with a difference of -0.68% (P = 0.8419), and the overall mortality during the 30-day follow-up period was 1.19% and 1.81% in the test and control group, respectively, showing no significant difference between the 2 groups (P= 0.6837), whereas the SAE incidence during the 12-month follow-up period was 12.50% and 17.47% in the test and control groups, respectively, which was not statistically significant (P=0.2222).

This trial showed that the Numen coil was noninferior to the Axium coil in terms of intracranial aneurysm embolization and can be considered as a safe and effective coil for treating patients with intracranial aneurysm in clinical practice.

This trial showed that the Numen coil was noninferior to the Axium coil in terms of intracranial aneurysm embolization and can be considered as a safe and effective coil for treating patients with intracranial aneurysm in clinical practice.

To determine preoperative 12-Item Short Form Health Survey (SF-12) Mental Component Summary (MCS) influence on minimally important clinical difference (MCID) and patient-reported outcome measures in patients with isthmic spondylolisthesis receiving minimally invasive transforaminal lumbar interbody fusion.

Patients with isthmic spondylolisthesis undergoing primary, single-level minimally invasive transforaminal lumbar interbody fusion at L5-S1 were retrospectively identified and divided into preoperative SF-12 MCS <50 and SF-12 MCS ≥50 groups. Visual analog scale (VAS) back/leg, Oswestry Disability Index (ODI), SF-12 Physical Composite Score (PCS), and Patient-Reported Outcome Measurement Information System physical function (PROMIS-PF) were assessed. Improvements from preoperative score were analyzed via paired samples t test. Patient-reported outcome measures and MCID attainment between groups were evaluated using linear regression and χ

, respectively.

SF-12 MCS <50 and SF-12 MCS ≥50 groups intioning.

Patients with SF-12 MCS less then 50 demonstrated fewer long-term improvements from preoperative to 2 years and inferior patient-reported outcome measures at most time points for pain and disability following minimally invasive transforaminal lumbar interbody fusion. MCID attainment largely did not differ by preoperative mental functioning.

The purpose of this bibliometric analysis was to explore disciplinary hotspots and collaborative networks in research on neuropathic pain (NPP) research in the past 20 years.

The articles related to NPP were obtained from Web of Science database. Global publications on neuropathic pain were analyzed in terms of different aspects such as number of papers, citation rates, authors, institutions, countries/regions, journals, and funding, as well as relevant partnerships and topic hotspots RESULTS From 2001 to 2020, 6905 articles related to NPP research were published worldwide. The number of publications had increased over the last 20 years continually. Pain was the most productive and the most frequently co-cited journal. Baron R was the most productive and influential author. The most productive country and institution were USA and Harvard University respectively. Researchers and institutions from the USA, Japan and China were the core research forces. There was a broad and close cooperation in the field worldwide. The top authors and top institutions had collaborated relatively closely with others.

The research of NPP is a well-developed and prospective field of medical study. Pain, European Journal of Pain, and Molecular Pain show more interested in this field. The USA, Harvard University, and Ralf Baron were the top country, institution, and author, respectively. Global research collaboration is extensive. Top institutions and authors had cooperation.

The research of NPP is a well-developed and prospective field of medical study. Pain, European Journal of Pain, and Molecular Pain show more interested in this field. The USA, Harvard University, and Ralf Baron were the top country, institution, and author, respectively. Global research collaboration is extensive. Top institutions and authors had cooperation.

The parasellar region is one of the most complex of the skull base. In this study, we review the anatomy and approaches to this region through a 360° perspective, correlating microsurgical and endoscopic anatomic nuances of this area.

An endoscopic endonasal approach (EEA) and microsurgical dissections were performed. The parasellar anatomy is reviewed and common areas of tumor extensions are assessed. Surgical approaches are discussed based on the anatomic nuances of those regions.

The cavernous sinus (CS) can be divided into 2 spaces posterosuperior, above and behind the internal carotid artery (ICA); and anterior, in front of the cavernous ICA. Those spaces can be approached through the CS walls anterior and/or medial wall via EEA; or superior and/or lateral wall via transcranial approaches. The relationship of the Meckel cave, adjacent to the lateral and posterior wall of the CS, is relevant for surgical planning. Areas often affected by tumor extension can be divided into 6 regions superior (cisternal), superolateral (parapeduncular), posterolateral (Meckel cave and petrous bone), medial (sella), anterior (superior orbital fissure), and anterior inferior (pterygopalatine fossa). Anatomic and technical nuances of each of those regions should be taken into consideration when dealing with tumors in the parasellar space.

A transcranial approach and EEA provide effective access to the parasellar region. Management of cavernous sinus and Meckel cave tumors requires familiarity with those approaches. Understanding of the surgical anatomy of the parasellar region, from above and below, is therefore necessary for adequate surgical planning and execution.

A transcranial approach and EEA provide effective access to the parasellar region. Management of cavernous sinus and Meckel cave tumors requires familiarity with those approaches. Understanding of the surgical anatomy of the parasellar region, from above and below, is therefore necessary for adequate surgical planning and execution.

Decompressive craniectomy (DC) is an established optional treatment for malignant hemispheric infarction (MHI). We analyzed relevant clinical factors and computed tomography (CT) measurements in patients with DC for MHI to identify predictors of functional outcome 3-6 months after stroke.

This study was performed at 2 comprehensive stroke centers. The inclusion criteria required DC for MHI, no additional intraoperative procedures (strokectomy or cerebral ventricular drain placement), and documented functional status 3-6 months after the stroke. We classified functional outcome as acceptable if the modified Rankin Scale score was <5, or as unacceptable if it was 5 or 6 (bedbound and totally dependent on others or death). Multiple logistic regression analyzed relevant clinical factors and multiple perioperative CT measurements to identify predictors of acceptable functional outcome.

Of 87 identified consecutive patients, 66 met the inclusion criteria. Acceptable functional outcome occurred in 35 of 66 (53%) patients. Likelihood of acceptable functional outcome decreased significantly with increasing age (OR 0.92, 95% CI 0.82-0.97, P= 0.004) and with increasing post-DC midline brain shift (OR 0.78, 95% CI 0.64-0.96, P= 0.016), and decreased non-significantly with left-sided stroke (OR 0.30, 95% CI 0.08-1.10, P= 0.069) and with increasing craniectomy barrier thickness (OR 0.92, 95% CI 0.85-1.01, P= 0.076).

Patient age and the post-DC midline shift may be useful in prognosticating functional outcome after DC for MHI. Stroke side and craniectomy barrier thickness merit further ideally prospective outcome prediction testing.

Patient age and the post-DC midline shift may be useful in prognosticating functional outcome after DC for MHI. Stroke side and craniectomy barrier thickness merit further ideally prospective outcome prediction testing.

A 3-column osteotomy is sometimes challenging in congenital kyphosis (CK) with many anterior unsegmented vertebrae (AUVs). This study compared surgical outcomes of single-level 3-column osteotomy and associated complications in CK with increasing number of AUVs.

We retrospectively reviewed 25 consecutive patients with AUVs in CK who underwent surgery at a mean age of 16.2 ± 10.3 years. Patients were stratified into 2 groups according to the number of AUVs 3 AUVs and ≥4 AUVs. Osteotomy types, surgical outcomes, and related complications were analyzed and compared between groups.

The 3 AUVs group comprised 13 patients, and the ≥4 AUVs group comprised 12 patients. Pedicle subtraction osteotomy, grade 4 osteotomy, vertebral column resection, and vertebral column decancellation accounted for 15.4%, 38.5%, 46.1%, and 0% of procedures in the 3 AUVs group and 8.3%, 0%, 83.3%, and 8.3% of procedures in the ≥4 AUVs group. Preoperative focal kyphosis, which was significantly higher in the ≥4 AUVs group (82.9° ± 28° vs. 59.7° ± 9.4°, P= 0.010), was corrected in both groups postoperatively. The ≥4 AUVs group had significantly higher remaining kyphosis (33.6° ± 13.4° vs. 15.1° ± 9.1°, P < 0.001) with a significantly lower correction rate (61.2% ± 13.6% vs. 75.0% ± 15.6%, P= 0.001). The complication rate, mainly involving vertebral subluxation and proximal junctional kyphosis, was significantly higher in the ≥4 AUVs group than the 3 AUVs group (8/12 vs. 1/13, P= 0.004).

Posterior single-level 3-column osteotomy can achieve satisfactory kyphosis correction in CK with 3 AUVs. Decreasing kyphosis correction and increasing surgery-related complications are prone to develop when treating CK with ≥4 AUVs.

Posterior single-level 3-column osteotomy can achieve satisfactory kyphosis correction in CK with 3 AUVs. Decreasing kyphosis correction and increasing surgery-related complications are prone to develop when treating CK with ≥4 AUVs.7-Nitro-2,1,3-benzoxadiazole (NBD) is an environmentally responsive fluorophore. We have reported that GIF2114 and GIF2115, anti-ferroptotic N,N-dimethylaniline-compounds, localize to lysosome when they are visualized by NBD. Here we show that the NBD fluorescence of GIF2259, a hybrid derivative of GIF2114 and GIF2115, was quenched in aqueous buffer. However, the fluorescence was recovered when GIF2259 was localized on lysosomes. Although the dimethylamine group of GIF2259 is not essential for the lysosome localization, it contributes to a high specific/nonspecific ratio of fluorescence. Under a normal condition, the lysosomal signal visualized by GIF2259 did not overlap with mitochondria, while, under starved or depolarization conditions, it overlapped with mitochondria, suggesting that GIF2259 could be used as a simple tool for monitoring lysosomal metabolism and mitochondrial turnover, that is mitophagy.